Picker K M, Mielck J B
Department of Pharmaceutical Technology, University of Hamburg, Germany.
Pharm Dev Technol. 1998 Feb;3(1):31-41. doi: 10.3109/10837459809028477.
The aim of this research was to investigate the elastic-plastic deformation behavior of the cellulose ethers hydroxypropylmethylcellulose (HPMC), hydroxyethylmethylcellulose (HEMC), and sodium carboxymethylcellulose (NaCMC) at relative humidities (RH) of 38, 57, and 75% and assess how the release of drugs embedded in such matrices is affected by the inner structure of the tablets formed during tabletting. Sorption and desorption isotherms and glass transition temperature were determined between 32 and 75% RH. The materials were equilibrated at 38, 57, and 75% RH and tabletted to a range of graded maximum relative densities. Pressure-time and displacement-time curves were analyzed by use of the Heckel function and a modified Weibull function (pressure-time only). After equilibration at the different RHs, all materials were in the glassy state. The respective degrees of polymerization had negligible effect on the absolute content of water, the sorption isotherms, and finally the densification behavior. At 38% RH, NaCMC contains the same amount of water as HPMC and HEMC, but deforms less plastically than the latter. This is attributed to tight binding of the water of hydration in the former. With increasing RH, NaCMC becomes only a little more plastic than both HPMC and HEMC, although it contains more than twice the amount of water. The binding strength of water and its molecular mobility, not the amount, seems to determine the readiness for volume reduction under load.
本研究的目的是研究羟丙基甲基纤维素(HPMC)、羟乙基甲基纤维素(HEMC)和羧甲基纤维素钠(NaCMC)这三种纤维素醚在38%、57%和75%相对湿度(RH)下的弹塑性变形行为,并评估压片过程中形成的此类基质中包埋药物的释放如何受到片剂内部结构的影响。在32%至75%相对湿度之间测定了吸附和解吸等温线以及玻璃化转变温度。将材料在38%、57%和75%相对湿度下平衡,并压制成一系列分级的最大相对密度。通过使用Heckel函数和修正的威布尔函数(仅压力-时间)分析压力-时间曲线和位移-时间曲线。在不同相对湿度下平衡后,所有材料均处于玻璃态。各自的聚合度对水的绝对含量、吸附等温线以及最终的致密化行为影响可忽略不计。在38%相对湿度下,NaCMC所含水量与HPMC和HEMC相同,但塑性变形比后两者小。这归因于前者中水合水的紧密结合。随着相对湿度的增加,尽管NaCMC所含水量是HPMC和HEMC的两倍多,但它的塑性仅比它们略高一点。水的结合强度及其分子流动性,而非水量,似乎决定了在负载下体积减小的难易程度。